Spasticity negatively influences quality of life. It causes pain and fatigue, disturbs sleep, restricts daily activities like walking, sitting, and bathng, and can complicate rehabilitation efforts. Management of muscle tone abnormalities is a serious challenge that is sometimes insurmountable. Thus, investigations designed to develop novel therapeutic interventions, such as those described in this proposal, have very high potential significance. This application aims to investigate effects of a new method that utilizes trans-spinal subthreshold direct current stimulation (tsDCS) to attenuate abnormal muscle tone in mice with spinal cord injury (SCI). Our laboratory is testing the general hypothesis that subthreshold direct current can modulate spinal excitability. We are performing parametric studies, including combination with other stimulation strategies, to optimize the effects of tsDCS. Our preliminary data are the first to show that applying spinal-sciatic direct current stimulation (DCS) can decrease or increase tonic or phasic stretch responses (depending on the direction of the current) in anesthetized SCI mice. This proposal aims to further investigate spinal-sciatic DCS in anesthetized and awake animals. The specific aims are to test: 1) long-term effects of longer duration spinal-sciatic DCS on muscle tone and cortical outputs in anesthetized SCI animals, 2) short-term effects of spino-sciatic DCS in awake animals with spasticity following contusive SCI, and 3) long-term effects of repetitive spinal-sciatic DCS on spasticity and recovery of skilled locomotion in animals with SCI. We have developed a testing system that can reliably measure spasticity, defined as velocity-dependent increase in muscle tone, in anesthetized mice, and we will use this proposal to adapt the system to measure spasticity in awake animals. An implantable system will be used to deliver repetitive spinal-sciatic DCS in awake animals. This approach is expected to permanently attenuate spasticity and improve recovery of skilled locomotion after SCI. Moreover, according to our preliminary results, the proposed approach can also be used to manage spasticity during the stimulation period because it does not block normal signals from the spinal cord or brain to muscle targets (e.g. during walking). The overarching goal is to demonstrate proof of concept, which will provide the basis to translate the proposed approach to humans to manage spasticity or restore normal muscle tone.